Leukocyte filtration and leukocyte modulation therapy during extracorporeal cardiopulmonary resuscitation in a porcine model of prolonged cardiac arrest. 2024

Jensyn J VanZalen, and Takahiro Nakashima, and Annie Phillips, and Joseph E Hill, and Angela J Westover, and Liandi Lou, and Jinhui Liao, and Joshua Mergos, and Garrett Fogo, and Thomas H Sanderson, and William C Stacey, and Mohamad Hakam Tiba, and David H Humes, and Robert H Bartlett, and Alvaro Rojas-Peña, and Robert W Neumar
Department of Surgery and ECLS Laboratory, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.

Extracorporeal cardiopulmonary resuscitation (ECPR) is emerging as a feasible and effective rescue strategy for prolonged cardiac arrest (CA). However, prolonged total body ischemia and reperfusion can cause microvascular occlusion that prevents organ reperfusion and recovery of function. One hypothesized mechanism of microvascular "no-reflow" is leukocyte adhesion and formation of neutrophil extracellular traps. In this study we tested the hypothesis that a leukocyte filter (LF) or leukocyte modulation device (L-MOD) could reduce NETosis and improve recovery of heart and brain function in a swine model of prolonged cardiac arrest treated with ECPR. Thirty-six swine (45.5 ± 2.5 kg, evenly distributed sex) underwent 8 min of untreated ventricular fibrillation CA followed by 30 min of mechanical CPR with subsequent 8 h of ECPR. Two females were later excluded from analysis due to CPR complications. Swine were randomized to standard care (Control group), LF, or L-MOD at the onset of CPR. NET formation was quantified by serum dsDNA and citrullinated histone as well as immunofluorescence staining of the heart and brain for citrullinated histone in the microvasculature. Primary outcomes included recovery of cardiac function based on cardiac resuscitability score (CRS) and recovery of neurologic function based on the somatosensory evoked potential (SSEP) N20 cortical response. In this model of prolonged CA treated with ECPR we observed significant increases in serum biomarkers of NETosis and immunohistochemical evidence of microvascular NET formation in the heart and brain that were not reduced by LF or L-MOD therapy. Correspondingly, there were no significant differences in CRS and SSEP recovery between Control, LF, and L-MOD groups 8 h after ECPR onset (CRS = 3.1 ± 2.7, 3.7 ± 2.6, and 2.6 ± 2.6 respectively; p = 0.606; and SSEP = 27.9 ± 13.0%, 36.7 ± 10.5%, and 31.2 ± 9.8% respectively, p = 0.194). In this model of prolonged CA treated with ECPR, the use of LF or L-MOD therapy during ECPR did not reduce microvascular NETosis or improve recovery of myocardial or brain function. The causal relationship between microvascular NETosis, no-reflow, and recovery of organ function after prolonged cardiac arrest treated with ECPR requires further investigation.

UI MeSH Term Description Entries
D007962 Leukocytes White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES). Blood Cells, White,Blood Corpuscles, White,White Blood Cells,White Blood Corpuscles,Blood Cell, White,Blood Corpuscle, White,Corpuscle, White Blood,Corpuscles, White Blood,Leukocyte,White Blood Cell,White Blood Corpuscle
D008297 Male Males
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D005260 Female Females
D006323 Heart Arrest Cessation of heart beat or MYOCARDIAL CONTRACTION. If it is treated within a few minutes, heart arrest can be reversed in most cases to normal cardiac rhythm and effective circulation. Asystole,Cardiac Arrest,Cardiopulmonary Arrest,Arrest, Cardiac,Arrest, Cardiopulmonary,Arrest, Heart,Asystoles
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013552 Swine Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA). Phacochoerus,Pigs,Suidae,Warthogs,Wart Hogs,Hog, Wart,Hogs, Wart,Wart Hog
D015199 Extracorporeal Membrane Oxygenation Application of a life support system that circulates the blood through an oxygenating system, which may consist of a pump, a membrane oxygenator, and a heat exchanger. Examples of its use are to assist victims of SMOKE INHALATION INJURY; RESPIRATORY FAILURE; and CARDIAC FAILURE. ECMO Extracorporeal Membrane Oxygenation,Oxygenation, Extracorporeal Membrane,Venoarterial ECMO,Venoarterial Extracorporeal Membrane Oxygenation,Venovenous ECMO,Venovenous Extracorporeal Membrane Oxygenation,ECLS Treatment,ECMO Treatment,Extracorporeal Life Support,ECLS Treatments,ECMO Treatments,ECMO, Venoarterial,ECMO, Venovenous,Extracorporeal Life Supports,Extracorporeal Membrane Oxygenations,Life Support, Extracorporeal,Membrane Oxygenation, Extracorporeal,Treatment, ECLS,Treatment, ECMO,Venoarterial ECMOs,Venovenous ECMOs
D016887 Cardiopulmonary Resuscitation The artificial substitution of heart and lung action as indicated for HEART ARREST resulting from electric shock, DROWNING, respiratory arrest, or other causes. The two major components of cardiopulmonary resuscitation are artificial ventilation (RESPIRATION, ARTIFICIAL) and closed-chest CARDIAC MASSAGE. Basic Cardiac Life Support,CPR,Code Blue,Mouth-to-Mouth Resuscitation,Cardio-Pulmonary Resuscitation,Life Support, Basic Cardiac,Cardio Pulmonary Resuscitation,Mouth to Mouth Resuscitation,Mouth-to-Mouth Resuscitations,Resuscitation, Cardio-Pulmonary,Resuscitation, Cardiopulmonary,Resuscitation, Mouth-to-Mouth,Resuscitations, Mouth-to-Mouth
D047589 Leukocyte Reduction Procedures The removal of LEUKOCYTES from BLOOD to reduce BLOOD TRANSFUSION reactions and lower the chance of transmitting VIRUSES. This may be performed by FILTRATION or by CYTAPHERESIS. Leukocyte Depletion Procedures,Leukocyte Reduction Filtration,Leukocyte Removal Procedures,Depletion Procedure, Leukocyte,Depletion Procedures, Leukocyte,Filtration, Leukocyte Reduction,Filtrations, Leukocyte Reduction,Leukocyte Depletion Procedure,Leukocyte Reduction Filtrations,Leukocyte Reduction Procedure,Leukocyte Removal Procedure,Procedure, Leukocyte Depletion,Procedure, Leukocyte Reduction,Procedure, Leukocyte Removal,Procedures, Leukocyte Depletion,Procedures, Leukocyte Reduction,Procedures, Leukocyte Removal,Reduction Filtration, Leukocyte,Reduction Filtrations, Leukocyte,Reduction Procedure, Leukocyte,Reduction Procedures, Leukocyte,Removal Procedure, Leukocyte,Removal Procedures, Leukocyte

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